Universality of the phenomenon of «neurotoxicity» (literature review)

Introduction. The neurotoxic effect is considered as one of the variants of the toxicity of many xenobiotics. Neurotoxic effects develop not only in poisoning, but also when exposed to biological (for example, pathogens of infectious diseases) and physical (for example, ionizing and non-ionizing radiation) factors. Materials and methods. The subject of the analysis was the phenomenon of neurotoxicity. The information was obtained by studying the databases Scopus, Web of Science, PubMed, RSCI. Results. The absence of a single definition of the concept of «neurotoxicant» is noted. In addition to chemicals, other factors have neurotoxicity: biological, physical. The mechanisms of neurodegeneration under the influence of neurotoxicants with different mechanisms of action are similar and include excitotoxicity, neuroinflammation, suppression of mitochondrial function, inhibition of neurogenesis and gliogenesis, oxidative stress, increased BBB permeability and apoptosis. The presented features allow us to speak about the universality of the phenomenon of «neurotoxicity». Conclusion. When considering the phenomenon of «neurotoxicity», certain difficulties arise. A clear idea of the etiological factors of this phenomenon is not fully formulated. A comprehensive classification of neurotoxicants has not been created. At the same time, the processes of neurodegeneration are very similar in cases of poisoning with neurotoxicants with different mechanisms of action, which proves the universality of the phenomenon of «neurotoxicity».

Pharmaceutical Products and Pesticides Toxicity Associated with Microplastics (Polyvinyl Chloride) in Artemia salina

Pharmaceutical products, as well as insecticides and antimicrobials, have been extensively studied, but knowledge of their effects—especially those caused by their mixtures with microplastics—on aquatic organisms remains limited. However, it should be borne in mind that the state of knowledge on acute and chronic effects in aquatic organisms for pharmaceuticals and pesticides is not similar. In response, this investigation analyzed the presence of microplastics (polyvinyl chloride) and their impacts on the toxicity of chlorpyrifos (an insecticide) and triclosan (an antibacterial) when they coincide in the environment, alongside the two most consumed drugs of their type (hypolipemic and anticonvulsant, respectively), namely simvastatin and carbamazepine, in Artemia salina. LC50 and cholinesterase enzyme activity were calculated to determine the possible neurotoxicity associated with emergent contaminants in the treatments. The LC50 values obtained were 0.006 mg/dm3 for chlorpyrifos, 0.012 mg/dm3 for chlorpyrifos associated with microplastics, 4.979 mg/dm3 for triclosan, 4.957 mg/dm3 for triclosan associated with microplastics, 9.35 mg/dm3 for simvastatin, 10.29 mg/dm3 for simvastatin associated with microplastics, 43.25 mg/dm3 for carbamazepine and 46.50 mg/dm3 for carbamazepine associated with microplastics in acute exposure. These results indicate that the presence of microplastics in the medium reduces toxicity, considering the LC50 values. However, exposure to chlorpyrifos and carbamazepine, both alone and associated with microplastics, showed a decline in cholinesterase activity, confirming their neurotoxic effect. Nevertheless, no significant differences were observed with the biomarker cholinesterase between the toxicant and the toxicant with microplastics.

LRRK2 along the Golgi and lysosome connection: a jamming situation

Parkinson's disease (PD) is an age-related neurodegenerative disorder, clinically characterized by bradykinesia, rigidity, and resting tremor. Leucine-Rich Repeat Kinase 2 (LRRK2) is a large, multidomain protein containing two enzymatic domains. Missense mutations in its coding sequence are amongst the most common causes of familial PD. The physiological and pathological impact of LRRK2 is still obscure, but accumulating evidence supports a role for LRRK2 in membrane and vesicle trafficking, mainly functioning in the endosome-recycling system, (synaptic) vesicle trafficking, autophagy, and lysosome biology. LRRK2 binds and phosphorylates key regulators of the endomembrane systems and is dynamically localized at the Golgi. The impact of LRRK2 on the Golgi may reverberate throughout the entire endomembrane system and occur in multiple intersecting pathways, including endocytosis, autophagy, and lysosomal function. This would lead to overall dysregulation of cellular homeostasis and protein catabolism, leading to neuronal dysfunction and accumulation of toxic protein species, thus underlying the possible neurotoxic effect of LRRK2 mutations causing PD.